The overall goal of this proposal is to examine the toxic and carcinogenic effects of estrogenic compounds on the neonatal reproductive tract. This will be done in an attempt to relate these neonatal events to the development of reproductive tract abnormalities in the adult animal. Estrogen induced patterns of uterotropic and vaginotropic responses will be examined in the normal adult rat. These patterns will be compared to those observed in animals which have received estrogens during the neonatal period. Response pattern analyses will include cytological changes, cell growth responses in vivo and in vitro and biochemical analysis of cellular proteins with special emphasis on vaginal keratins and estrogen receptors. Estrogen induced patterns of uterotropic and vaginotropic responses will also be examined during the neonatal period. This will be done in order to detect specific or distinct patterns of response induced by various estrogenic agents, such as DES, kepone and o,p', DDT. The protective effect of progesterone in the neonatal rat exposed to estrogens will also be examined. Alterations in estrogen induced patterns in these animals will be compared with those receiving estrogens alone. The identification of distinct estrogen induced patterns of response which can be associated with the occurrence of reproductive tract teratologies and neoplasia would be of considerable importance as a predictive screening test for environmental toxins and carcinogens. In addition, knowledge of such "abnormal patterns" could help to define the relationships that exists between estrogenicity, teratogenicity and carcinogenicity.